scholarly journals Transferrin: physiologic behavior and clinical implications

Blood ◽  
1984 ◽  
Vol 64 (4) ◽  
pp. 763-767 ◽  
Author(s):  
HA Huebers ◽  
CA Finch
Keyword(s):  
Iron Uptake ◽  
Iron Transport ◽  
Regulatory Mechanism ◽  
Effective Means ◽  
Molecular Defect ◽  
Life Saving ◽  
Receptor Number ◽  
Idiopathic Hemochromatosis ◽  
Definition Of ◽  
Diferric Transferrin

The transferrin iron transport system, along with its procurement sites and delivery receptors, provides a highly effective means of satisfying internal iron requirements. Iron uptake by individual tissues is determined by their receptor number, by the relative amounts of monoferric and diferric transferrin in circulation, and by the amount of available iron in donor tissues. Although the modus operandi of this system under basal conditions has been characterized, its exquisite regulation remains an enigma. In some manner, the procurement of iron is determined by iron requirements. What seems to be an inappropriate behavior of the absorptive mechanism in thalassemia and certain other erythroid overload states may actually be life-saving in the absence of transfusion, since it results in higher levels of plasma iron and thereby higher levels of erythropoiesis. The definition of the regulatory mechanism in such conditions may well lead to an understanding of the molecular defect in idiopathic hemochromatosis.

scholarly journals Transferrin: physiologic behavior and clinical implications

Blood ◽  
1984 ◽  
Vol 64 (4) ◽  
pp. 763-767 ◽  
Author(s):  
HA Huebers ◽  
CA Finch
Keyword(s):  
Iron Uptake ◽  
Iron Transport ◽  
Regulatory Mechanism ◽  
Effective Means ◽  
Molecular Defect ◽  
Life Saving ◽  
Receptor Number ◽  
Idiopathic Hemochromatosis ◽  
Definition Of ◽  
Diferric Transferrin

Abstract The transferrin iron transport system, along with its procurement sites and delivery receptors, provides a highly effective means of satisfying internal iron requirements. Iron uptake by individual tissues is determined by their receptor number, by the relative amounts of monoferric and diferric transferrin in circulation, and by the amount of available iron in donor tissues. Although the modus operandi of this system under basal conditions has been characterized, its exquisite regulation remains an enigma. In some manner, the procurement of iron is determined by iron requirements. What seems to be an inappropriate behavior of the absorptive mechanism in thalassemia and certain other erythroid overload states may actually be life-saving in the absence of transfusion, since it results in higher levels of plasma iron and thereby higher levels of erythropoiesis. The definition of the regulatory mechanism in such conditions may well lead to an understanding of the molecular defect in idiopathic hemochromatosis.

scholarly journals Iron distribution in Belgrade rat reticulocytes after inhibition of heme synthesis with succinylacetone

Blood ◽  
1993 ◽  
Vol 81 (12) ◽  
pp. 3414-3421 ◽  
Author(s):  
LM Garrick ◽  
K Gniecko ◽  
Y Liu ◽  
DS Cohan ◽  
JA Grasso ◽  
...  
Keyword(s):  
Iron Uptake ◽  
Iron Transport ◽  
Aminolevulinic Acid ◽  
Specific Inhibitor ◽  
Hypochromic Anemia ◽  
Endocytic Vesicle ◽  
Heme Synthesis ◽  
Diferric Transferrin ◽  
Rat Reticulocytes ◽  
Insight Into

Abstract We have used succinylacetone (4,6-dioxoheptanoic acid), a specific inhibitor of delta-aminolevulinic acid dehydrase, to gain insight into the defect in iron metabolism in the Belgrade anemia. The Belgrade rat has an inherited microcytic, hypochromic anemia associated with poor iron uptake into developing erythroid cells. Succinylacetone inhibits heme synthesis, leading to nonheme iron accumulation in mitochondria and cytosol of normal reticulocytes. When succinylacetone is used to inhibit Belgrade heme synthesis, iron from diferric transferrin does not accumulate in the stromal fraction that contains mitochondria, nor does 59Fe accumulate in the nonheme cytosolic fraction. Hence, the defect in the Belgrade rat reticulocyte occurs in the endocytic vesicle or in a step subsequent to iron transit from the vesicle but before the nonheme cytosolic or mitochondrial iron fractions. Therefore, the mutation affects either the release of iron from transferrin or iron transport from the vesicle to the mitochondrion.

scholarly journals Iron distribution in Belgrade rat reticulocytes after inhibition of heme synthesis with succinylacetone

Blood ◽  
1993 ◽  
Vol 81 (12) ◽  
pp. 3414-3421 ◽  
Author(s):  
LM Garrick ◽  
K Gniecko ◽  
Y Liu ◽  
DS Cohan ◽  
JA Grasso ◽  
...  
Keyword(s):  
Iron Uptake ◽  
Iron Transport ◽  
Aminolevulinic Acid ◽  
Specific Inhibitor ◽  
Hypochromic Anemia ◽  
Endocytic Vesicle ◽  
Heme Synthesis ◽  
Diferric Transferrin ◽  
Rat Reticulocytes ◽  
Insight Into

We have used succinylacetone (4,6-dioxoheptanoic acid), a specific inhibitor of delta-aminolevulinic acid dehydrase, to gain insight into the defect in iron metabolism in the Belgrade anemia. The Belgrade rat has an inherited microcytic, hypochromic anemia associated with poor iron uptake into developing erythroid cells. Succinylacetone inhibits heme synthesis, leading to nonheme iron accumulation in mitochondria and cytosol of normal reticulocytes. When succinylacetone is used to inhibit Belgrade heme synthesis, iron from diferric transferrin does not accumulate in the stromal fraction that contains mitochondria, nor does 59Fe accumulate in the nonheme cytosolic fraction. Hence, the defect in the Belgrade rat reticulocyte occurs in the endocytic vesicle or in a step subsequent to iron transit from the vesicle but before the nonheme cytosolic or mitochondrial iron fractions. Therefore, the mutation affects either the release of iron from transferrin or iron transport from the vesicle to the mitochondrion.

scholarly journals Antibodies to the Iron Uptake ABC Transporter Lipoproteins PiaA and PiuA Promote Opsonophagocytosis of Streptococcus pneumoniae

2005 ◽  
Vol 73 (10) ◽  
pp. 6852-6859 ◽  
Author(s):  
Maha Jomaa ◽  
Jose Yuste ◽  
James C. Paton ◽  
Christopher Jones ◽  
Gordon Dougan ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Abc Transporters ◽  
Iron Uptake ◽  
Iron Transport ◽  
Antibody Responses ◽  
Igg Subclass ◽  
Specific Enzyme ◽  
Low Levels ◽  
Passive Vaccination ◽  
Neutrophil Cell

ABSTRACT PiaA and PiuA are the lipoprotein components of the Pia and Piu Streptococcus pneumoniae iron uptake ABC transporters and are required for full virulence in mouse models of infection. Active or passive vaccination with recombinant PiuA and PiaA protects mice against invasive S. pneumoniae disease. In this study we have analyzed the antibody responses and mechanism of protection induced by PiuA and PiaA in more detail. For both proteins, two booster vaccinations induced stronger antibody responses in mice than a single or no booster vaccinations, and 5 μg of protein induced similar levels of antibody responses as 20 μg. Immunoglobulin G (IgG) subclass-specific enzyme-linked immunosorbent assays demonstrated that the antibody response to PiuA and PiaA was predominantly IgG1, with induction of only low levels of IgG2a. Anti-PiaA and anti-PiuA polyclonal rabbit antibodies bound to the surface of live S. pneumoniae when assessed by flow cytometry but did not inhibit growth of S. pneumoniae in cation-depleted medium or bacterial susceptibility to the iron-dependent antibiotic streptonigrin. However, anti-PiaA and anti-PiuA did increase complement-independent and -dependent opsonophagocytosis of different serotypes of S. pneumoniae by the human neutrophil cell line HL60. Hence, vaccination with PiaA and PiuA protects against S. pneumoniae infection by inducing antibodies that promote bacterial opsonophagocytosis rather than inhibiting iron transport.

Copper repletion enhances apical iron uptake and transepithelial iron transport by Caco-2 cells

2002 ◽  
Vol 282 (3) ◽  
pp. G527-G533 ◽  
Author(s):  
Okhee Han ◽  
Marianne Wessling-Resnick
Keyword(s):  
Iron Uptake ◽  
Iron Transport ◽  
Cell Monolayer ◽  
Transepithelial Transport ◽  
Apical Surface ◽  
Divalent Metal Transporter 1 ◽  
Divalent Metal Transporter ◽  
Metal Transporter ◽  
Copper Status ◽  
Copper Supplementation

The influence of copper status on Caco-2 cell apical iron uptake and transepithelial transport was examined. Cells grown for 7–8 days in media supplemented with 1 μM CuCl2had 10-fold higher cellular levels of copper compared with control. Copper supplementation did not affect the integrity of differentiated Caco-2 cell monolayers grown on microporous membranes. Copper-repleted cells displayed increased uptake of iron as well as increased transport of iron across the cell monolayer. Northern blot analysis revealed that expression of the apical iron transporter divalent metal transporter-1 (DMT1), the basolateral transporter ferroportin-1 (Fpn1), and the putative ferroxidase hephaestin (Heph) was upregulated by copper supplementation, whereas the recently identified ferrireductase duodenal cytochrome b (Dcytb) was not. These results suggest that DMT1, Fpn1, and Heph are involved in the iron uptake process modulated by copper status. Although a clear role for Dcytb was not identified, an apical surface ferrireductase was modulated by copper status, suggesting that its function also contributes to the enhanced iron uptake by copper-repleted cells. A model is proposed wherein copper promotes iron depletion of intestinal Caco-2 cells, creating a deficiency state that induces upregulation of iron transport factors.

Evidence for a copper-dependent iron transport system in the marine, magnetotactic bacterium strain MV-1

Microbiology ◽  
2004 ◽  
Vol 150 (9) ◽  
pp. 2931-2945 ◽  
Author(s):  
Bradley L. Dubbels ◽  
Alan A. DiSpirito ◽  
John D. Morton ◽  
Jeremy D. Semrau ◽  
J. N. E. Neto ◽  
...  
Keyword(s):  
Iron Content ◽  
Iron Uptake ◽  
Iron Transport ◽  
Dna Analysis ◽  
Iron Concentration ◽  
Protein A ◽  
Uptake System ◽  
Iron Uptake System ◽  
Cellular Iron ◽  
Solid Media

Cells of the magnetotactic marine vibrio, strain MV-1, produce magnetite-containing magnetosomes when grown anaerobically or microaerobically. Stable, spontaneous, non-magnetotactic mutants were regularly observed when cells of MV-1 were cultured on solid media incubated under anaerobic or microaerobic conditions. Randomly amplified polymorphic DNA analysis showed that these mutants are not all genetically identical. Cellular iron content of one non-magnetotactic mutant strain, designated MV-1nm1, grown anaerobically, was ∼20- to 80-fold less than the iron content of wild-type (wt) MV-1 for the same iron concentrations, indicating that MV-1nm1 is deficient in some form of iron uptake. Comparative protein profiles of the two strains showed that MV-1nm1 did not produce several proteins produced by wt MV-1. To understand the potential roles of these proteins in iron transport better, one of these proteins was purified and characterized. This protein, a homodimer with an apparent subunit mass of about 19 kDa, was an iron-regulated, periplasmic protein (p19). Two potential ‘copper-handling’ motifs (MXM/MX2M) are present in the amino acid sequence of p19, and the native protein binds copper in a 1 : 1 ratio. The structural gene for p19, chpA (copper handling protein) and two other putative genes upstream of chpA were cloned and sequenced. These putative genes encode a protein similar to the iron permease, Ftr1, from the yeast Saccharomyces cerevisiae, and a ferredoxin-like protein of unknown function. A periplasmic, copper-containing, iron(II) oxidase was also purified from wt MV-1 and MV-1nm1. This enzyme, like p19, was regulated by media iron concentration and contained four copper atoms per molecule of enzyme. It is hypothesized that ChpA, the iron permease and the iron(II) oxidase might have analogous functions for the three components of the S. cerevisiae copper-dependent high-affinity iron uptake system (Ctr1, Ftr1 and Fet3, respectively), and that strain MV-1 may have a similar iron uptake system. However, iron(II) oxidase purified from both wt MV-1 and MV-1nm1 displayed comparable iron oxidase activities using O2 as the electron acceptor, indicating that ChpA does not supply the multi-copper iron(II) oxidase with copper.

scholarly journals Genes Essential to Iron Transport in the Cyanobacterium Synechocystis sp. Strain PCC 6803

2001 ◽  
Vol 183 (9) ◽  
pp. 2779-2784 ◽  
Author(s):  
Hirokazu Katoh ◽  
Natsu Hagino ◽  
Arthur R. Grossman ◽  
Teruo Ogawa
Keyword(s):  
Iron Uptake ◽  
Iron Transport ◽  
Ferric Iron ◽  
Iron Acquisition ◽  
Complete Medium ◽  
Iron Starvation ◽  
Transporter Family ◽  
Genes Encoding ◽  
In Cells ◽  
Pcc 6803

ABSTRACT Genes encoding polypeptides of an ATP binding cassette (ABC)-type ferric iron transporter that plays a major role in iron acquisition inSynechocystis sp. strain PCC 6803 were identified. These genes are slr1295, slr0513, slr0327, and recently reportedsll1878 (Katoh et al., J. Bacteriol. 182:6523–6524, 2000) and were designated futA1, futA2, futB, andfutC, respectively, for their involvement in ferric iron uptake. Inactivation of these genes individually or futA1and futA2 together greatly reduced the activity of ferric iron uptake in cells grown in complete medium or iron-deprived medium. All the fut genes are expressed in cells grown in complete medium, and expression was enhanced by iron starvation. ThefutA1 and futA2 genes appear to encode periplasmic proteins that play a redundant role in iron binding. The deduced products of futB and futC genes contain nucleotide-binding motifs and belong to the ABC transporter family of inner-membrane-bound and membrane-associated proteins, respectively. These results and sequence similarities among the four genes suggest that the Fut system is related to the Sfu/Fbp family of iron transporters. Inactivation of slr1392, a homologue offeoB in Escherichia coli, greatly reduced the activity of ferrous iron transport. This system is induced by intracellular low iron concentrations that are achieved in cells exposed to iron-free medium or in the fut-less mutants grown in complete medium.

scholarly journals P007: A comparative analysis of qSOFA, SIRS and Early Warning Scores Criteria to identify sepsis in the prehospital setting

CJEM ◽  
2017 ◽  
Vol 19 (S1) ◽  
pp. S79-S80 ◽  
Author(s):  
S. AlQahtani ◽  
P. Menzies ◽  
B. Bigham ◽  
M. Welsford
Keyword(s):  
Severe Sepsis ◽  
Screening Tool ◽  
Early Recognition ◽  
Capture Rate ◽  
Data Capture ◽  
Prehospital Setting ◽  
Life Saving ◽  
Data Points ◽  
And Performance ◽  
Definition Of

Introduction: Early recognition of sepsis is key in delivering timely life-saving interventions. The role of paramedics in recognition of these patients is understudied. It is not known if the usual prehospital information gathered is sufficient for severe sepsis recognition. We sought to: 1) evaluate the paramedic medical records (PMRs) of severe sepsis patients to describe epidemiologic characteristics; 2) determine which severe sepsis recognition and prediction scores are routinely captured by paramedics; and 3) determine how these scores perform in the prehospital setting. Methods: We performed a retrospective review of patients ≥18 years who met the definition of severe sepsis in one of two urban Emergency Departments (ED) and had arrived by ambulance over an eighteen-month period. PMRs were evaluated for demographic, physiologic and clinical variables. The information was entered into a database, which auto-filled a tool that determined SIRS criteria, shock index, prehospital critical illness score, NEWS, MEWS, HEWS, MEDS and qSOFA. Descriptive statistics were calculated. Results: We enrolled 298 eligible sepsis patients: male 50.3%, mean age 73 years, and mean prehospital transportation time 30 minutes. Hospital mortality was 37.5%. PMRs captured initial: respiratory rate 88.6%, heart rate 90%, systolic blood pressure 83.2%, oxygen saturation 59%, temperature 18.7%, and Glasgow Coma Scale 89%. Although complete MEWS and HEWS data capture rate was <17%, 98% and 68% patients met the cut-point defining “critically-unwell” (MEWS ≥3) and “trigger score” (HEWS ≥5), respectively. The qSOFA criteria were completely captured in 82% of patients; however, it was positive in only 36%. It performed similarly to SIRS, which was positive in only 34% of patients. The other scores were interim in having complete data captured and performance for sepsis recognition. Conclusion: Patients transported by ambulance with severe sepsis have high mortality. Despite the variable rate of data capture, PMRs include sufficient data points to recognize prehospital severe sepsis. A validated screening tool that can be applied by paramedics is still lacking. qSOFA does not appear to be sensitive enough to be used as a prehospital screening tool for deadly sepsis, however, MEWS or HEWS may be appropriate to evaluate in a large prospective study.

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